Overexpression of the Anthocyanidin Synthase Gene in Strawberry Enhances Antioxidant Capacity and Cytotoxic Effects on Human Hepatic Cancer Cells

J Agric Food Chem. 2018 Jan 24;66(3):581-592. doi: 10.1021/acs.jafc.7b04177. Epub 2018 Jan 8.

Abstract

Food fortification through the increase and/or modulation of bioactive compounds has become a major goal for preventing several diseases, including cancer. Here, strawberry lines of cv. Calypso transformed with a construct containing an anthocyanidin synthase (ANS) gene were produced to study the effects on anthocyanin biosynthesis, metabolism, and transcriptome. Three strawberry ANS transgenic lines (ANS L5, ANS L15, and ANS L18) were analyzed for phytochemical composition and total antioxidant capacity (TAC), and their fruit extracts were assessed for cytotoxic effects on hepatocellular carcinoma. ANS L18 fruits had the highest levels of total phenolics and flavonoids, while those of ANS L15 had the highest anthocyanin concentration; TAC positively correlated with total polyphenol content. Fruit transcriptome was also specifically affected in the polyphenol biosynthesis and in other related metabolic pathways. Fruit extracts of all lines exerted cytotoxic effects in a dose/time-dependent manner, increasing cellular apoptosis and free radical levels and impairing mitochondrial functionality.

Keywords: RNA-seq; ROS; anthocyanidin synthase; anticancer effects; apoptosis; flavonoids; mitochondrial functionality; strawberry; transcriptome.

MeSH terms

  • Anthocyanins / analysis
  • Anthocyanins / biosynthesis
  • Anthocyanins / pharmacology
  • Antioxidants / analysis*
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Apoptosis
  • Fragaria / chemistry
  • Fragaria / enzymology*
  • Fragaria / genetics
  • Fruit / chemistry*
  • Fruit / enzymology
  • Fruit / genetics
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / physiopathology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxygenases / genetics*
  • Oxygenases / metabolism
  • Plant Proteins / genetics*
  • Plant Proteins / metabolism
  • Polyphenols / analysis
  • Polyphenols / metabolism
  • Polyphenols / pharmacology

Substances

  • Anthocyanins
  • Antioxidants
  • Plant Proteins
  • Polyphenols
  • Oxygenases
  • anthocyanidin synthase